Liquid Biopsy Following BBB Disruption Using Barrier Disrupting Fields in Patients Undergoing Spine Surgery

Summary

Objective: To identify new central nervous system (CNS) biomarkers to be used for blood-derived liquid biopsy once the blood-brain barrier (BBB), specifically the blood-arachnoid barrier (BAB), has been transiently disrupted by BDF in patients undergoing spine surgery.

Design: Single center (Sheba Medical Center), prospective, controlled. Phase: Feasibility study

Endpoints:

Efficacy The primary endpoint of the study is the elevation in blood concentration of CNS biomarkers following the study procedure compared to biomarkers detected in cerebrospinal fluid (CSF) of the same subject.

Safety The primary safety endpoint will be the overall incidence of BDF procedure-related AEs and SAEs, with severity graded according to CTCAE v5.0 criteria.

Study population:

The study population will include up to 20 patients undergoing spine surgery.

Study period:

24 months.

Inclusion criteria:

1. Adult subjects over the age of 18
2. Able to sign informed consent
3. Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring.

Exclusion criteria:

1. Pacemakers, or other implanted electric medical devices
2. Pregnant or lactating females
3. Major medical, neurologic or psychiatric condition who are judged as unable to fully comply with the study
4. History of skull fractures or previous brain surgery
5. American Society of Anesthesiologists grade \>2
6. Anticoagulants treatment
7. Damage to the dura resulting in CSF leak
8. Patients with seizures/epilepsy

Study procedure:

1. Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring will be enrolled in the study prior to surgery.
2. The patient will undergo preparation for surgery according to the standard care.
3. Once anesthetized and intubated, electrodes will be attached to the patient's head.
4. After placing the electrodes, when the patient is under anesthesia, a blood sample will be taken prior to BDF. This sample will be used as baseline for BDF.
5. The patient will then undergo a BDF procedure.
6. Additional blood samples will be taken for identification of CNS biomarkers.
7. Surgery will then proceed according to the standard of care.
8. Once the dura is opened, a CSF sample will be taken, in order to compare the blood biomarkers of the specific subject with the CSF biomarkers.
9. The surgery will continue according to the standard of care.

Conditions

• Spinal Tumors

Interventions

PROCEDURE

spinal surgery

Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring will be enrolled in the study prior to surgery. The patient will undergo preparation for surgery according to the standard care. Once anesthetized and intubated, electrodes will be attached to the patient's head. After placing the electrodes, when the patient is under anesthesia, a blood sample will be taken prior to BDF. This sample will be used as baseline for BDF. The patient will then undergo a BDF procedure. Additional blood samples will be taken for identification of CNS biomarkers. Surgery will then proceed according to the standard of care. Once the dura is opened, a CSF sample will be taken. The surgery will continue according to the standard of care

DEVICE

BDF

electrodes couples (voltage and ground) will be placed on the patient head and will be connected to a pulse generator. 2 electrodes couples will be activated in parallel, up to 8 electrodes couples total. EEG will be acquired after each series of pulses for a few sec.

Sponsors & Collaborators

• Sheba Medical Center

  lead OTHER_GOV

Principal Investigators

• Ran Harel, MD · Sheba Medical Center

• Yael Mardor, PhD · Sheba Medical Center

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-10-16

Primary Completion

2027-10-31

Completion

2027-10-31

FDA Device

Yes

Countries

• Israel

Study Locations